3 research outputs found
Long-resident droplets at the stratocumulus top
No full textTurbulence models predict low droplet-collision rates in stratocumulus
clouds, which should imply a narrow droplet size distribution and little
rain. Contrary to this expectation, rain is often observed in stratocumuli.
In this paper, we explore the hypothesis that some droplets can grow well
above the average because small-scale turbulence allows them to reside at
cloud top for a time longer than the convective-eddy time t*.
Long-resident droplets can grow larger because condensation due to longwave
radiative cooling, and collisions have more time to enhance droplet growth.
We investigate the trajectories of 1 billion Lagrangian droplets in direct
numerical simulations of a cloudy mixed-layer configuration that is based on
observations from the flight 11 from the VERDI campaign. High resolution is
employed to represent a well-developed turbulent state at cloud top. Only
one-way coupling is considered. We observe that 70 % of the droplets spend
less than 0.6t* at cloud top before leaving the cloud, while 15 % of
the droplets remain at least 0.9t* at cloud top. In addition, 0.2 % of
the droplets spend more than 2.5t* at cloud top and decouple from the
large-scale convective eddies that brought them to the top, with the result
that they become memoryless. Modeling collisions like a Poisson process leads
to the conclusion that most rain droplets originate from those memoryless
droplets. Furthermore, most long-resident droplets accumulate at the
downdraft regions of the flow, which could be related to the closed-cell
stratocumulus pattern. Finally, we see that condensation due to longwave
radiative cooling considerably broadens the cloud-top droplet size
distribution: 6.5 % of the droplets double their mass due to radiation in
their time at cloud top. This simulated droplet size distribution matches the
flight measurements, confirming that condensation due to longwave radiation
can be an important mechanism for broadening the droplet size distribution in
radiatively driven stratocumuli
Low level of exosomal long non-coding RNA HOTTIP is a prognostic biomarker in colorectal cancer
No full textMolecular risk stratification of colorectal cancer can improve patient outcome. A panel of lncRNAs (H19, HOTTIP, HULC and MALAT1) derived from serum exosomes of patients with non-metastatic CRC and healthy donors was analyzed. Exosomes from healthy donors carried significantly more H19, HULC and HOTTIP transcripts in comparison to CRC patients. Correlation analysis between lncRNAs and clinical data revealed a statistical significance between low levels of exosomal HOTTIP and poor overall survival. This was confirmed by multivariate analysis that HOTTIP is an independent prognostic marker for overall survival (HR: 4.5, CI: 1.69–11.98, p = 0.0027). Here, HOTTIP poses to be a valid biomarker for patients with a CRC to predict post-surgical survival time. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group
ВАРИАНТЫ И ПЕРСПЕКТИВЫ ПЕРЕПРОФИЛИРОВАНИЯ ЛЕКАРСТВЕННЫХ ПРЕПАРАТОВ ДЛЯ ИСПОЛЬЗОВАНИЯ В ТЕРАПИИ ОНКОЛОГИЧЕСКИХ ЗАБОЛЕВАНИЙ
No full textRecently many new approaches for repurposing or repositioning of the clinically used drugs have been developed. Drug repurposing allows not only to use known schemes for the synthesis of biologically active compounds, but also to avoid multiple studies that are necessary for drug approval process – analysis of pharmacokinetics, carcinogenicity, acute and chronic toxicity, including cardiotoxicity, nephrotoxicity, allergenicity etc. It makes possible to reduce the number of experimental studies as well as costs of investigations. In cancer research drug repurposing includes screening for medicines used nowadays for the treatment of patients with non-cancer diseases which possess anticancer activity or able to enhance the effects of the standard anticancer chemotherapy, and search for new applications of known anticancer drugs for the treatment of different cancer types. Scientific rationale for the search of the compounds with potential anticancer properties among drugs with different applications is based on the multiple cross-talks of signaling pathways, which can inhibit cell proliferation. Modern advances in genomics, proteomics and bioinformatics, development of permanently improving databases of drug molecular effects and high throughput analytical systems allow researchers to analyze simultaneously a large bulk of existing drugs and specific molecular targets. This review describes the main approaches and resources currently used for the drug repurposing, as well as a number of examples.В настоящее время появились новые программы по перепрофилированию или перепозиционированию лекарственных средств, используемых в медицинской практике. Перепрофилирование препаратов позволяет не только использовать отработанные схемы синтеза биологически активных соединений, но и избежать проведения исследований, необходимых для внедрения новых лекарственных препаратов в медицинскую практику, по фармакокинетике, канцерогенности, острой и хронической токсичности, в том числе кардиотоксичности, нефротоксичности, аллергенности и т.д. Это создает возможность сократить объем необходимых исследований и снизить затраты на них. В онкологии программы перепрофилирования лекарственных средств включают как поиск препаратов, обладающих противоопухолевой активностью или потенцирующих действие противоопухолевых препаратов, среди известных и широко применяемых лекарственных средств, используемых для лечения неонкологических заболеваний, так и анализ возможности использования уже известных противоопухолевых препаратов для лечения каких-либо новых нозологических форм заболевания. Основанием для поиска противоопухолевых свойств среди препаратов иного назначения является тот факт, что сигнальные пути в клетке характеризуются большим количеством перекрестных взаимодействий и некоторые из них могут ингибировать пролиферацию опухолевых клеток. Современные достижения геномики, протеомики, биоинформатики, появление объемных баз данных по молекулярным эффектам лекарственных препаратов, мощных аналитических систем и их постоянное совершенствование уже позволяет исследователям одновременно проанализировать большое количество существующих препаратов в применении к конкретной молекулярной мишени. В обзоре рассмотрены основные подходы и ресурсы, использующиеся в настоящее время для перепрофилирования лекарственных препаратов, а также приведен ряд примеров
